N-Fmoc-4-(tert-butoxycarbonyl-difluoro-methyl)-L-phenylalanine | 222843-03-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-Fmoc-4-(tert-butoxycarbonyl-difluoro-methyl)-L-phenylalanine
• 英文别名: (2S)-3-[4-[1,1-difluoro-2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]phenyl]-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid
• CAS: 222843-03-0
• 化学式: C₃₀H₂₉F₂NO₆
• 分子量: 537.56
• InChiKey: UGKIKJQSTOAAJX-VWLOTQADSA-N

物化性质

• 沸点：
  687.1±55.0 °C(Predicted)
• 密度：
  1.287±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Fmoc-L-亮氨酸 、 N-Fmoc-4-(tert-butoxycarbonyl-difluoro-methyl)-L-phenylalanine 、 alkaline earth salt of/the/ methylsulfuric acid 生成 (S)-4-{(S)-1-((S)-1-Carbamoyl-3-methyl-butylcarbamoyl)-2-[4-(carboxy-difluoro-methyl)-phenyl]-ethylcarbamoyl}-4-(9H-fluoren-9-ylmethoxycarbonylamino)-butyric acid
  参考文献：
  名称：

  Tripeptide inhibitors of Yersinia protein-tyrosine phosphatase

  摘要：

  The protein-tyrosine phosphatase (PTP) 'YopH' is a virulence factor of Yersinia pestis, the causative agent of plague. Potential use of Yersinia as a bioterrorism agent renders YopH inhibitors of therapeutic importance. Previously, we had examined the inhibitory potencies of a variety of phosphotyrosyl (pTyr) mimetics against the human PTP1B enzyme by displaying them in the EGFR-derived hexapeptide sequence, 'Ac-Asp-Ala-Asp-Glu-Xxx-Leu-amide', where Xxx=pTyr mimetic. The poor inhibitory potencies of certain of these pTyr mimetics were attributed to restricted orientation within the PTP1B catalytic pocket incurred by extensive peripheral interaction of the hexapeptide platform. Utilizing the smaller tripeptide platform. 'Fmoc-Glu-Xxx-Leu-amide' we demonstrate herein that several of the low affinity hexapeptide-expressed pTyr mimetics exhibit high PTP1B affinity within the context of the tripeptide platform. Of particular note, the mono-anionic 4(carboxydifluoroinethyl)Phe residue exhibits affinity equivalent to the di-anionic F(2)Pmp residue, which had previously been among the most potent PTP-binding motifs. Against YopH, it was found that all tripeptides having Gin residues with an unprotected side chain carboxyl were inactive. Alternatively, in their Glu-OBn ester forms, several of the tripeptides exhibited good YopH affinity with the mono-anionic peptide, Fmoc-Glu(OBn)-Xxx-Leu-amide, where Xxx = 4-(carboxymethyloxy)Phe providing an IC50 value of 2.8 muM. One concern with such inhibitors is that they may potentially function by non-specific mechanisms. Studies with representative inhibitors. while failing to provide evidence of a non-specific promiscuous mode of inhibition, did indicate that non-classical inhibition may be involved. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00481-5
• 作为产物：
  描述：

  4-(bromomethyl)-α,α-difluorobenzeneacetic acid 1,1-dimethylethyl ester 在 钯 氢气 、 碳酸氢钠 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 六甲基磷酰三胺 、 水 为溶剂， 反应 23.5h， 生成 N-Fmoc-4-(tert-butoxycarbonyl-difluoro-methyl)-L-phenylalanine
  参考文献：
  名称：

  Synthesis of Fmoc-protected 4-carboxydifluoromethyl-L-phenylalanine: A phosphotyrosyl mimetic of potential use for signal transduction studies

  摘要：

  4-(Carboxymethyl)phenylalanine (2) and its alpha,alpha-difluoro homologue 4-(carboxydifluoromethyl)-phenylalanine (3) have been described as phosphotyrosyl mimetics. Herein we report the synthesis of N-Fmoc 4-(0-tert-butyl carboxymethyl)-phenylalanine (4) and N-Fmoc 4-(0-tert-butyl carboxydifluoromethyl)phenylalanine (5) in high enantiomeric purity. These analogues bear orthogonal protection suitable for the preparation of inhibitors directed against a variety of signal transduction pathways, including SH2 and PTP domains and protein-tyrosine phosphatases. Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4020(99)00076-9